Ghorbani Fatemeh, Osatd-Rahimi Negar, Mansouritorghabeh Fatemeh, Ebrahimzadeh-Bideskan Alireza, Saburi Ehsan, Rajabian Arezoo, Hosseini Mahmoud
Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.
Department of Anatomy and Cell Biology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, I.R. Iran.
Res Pharm Sci. 2025 Mar 31;20(2):218-229. doi: 10.4103/RPS.RPS_187_23. eCollection 2025 Apr.
Melatonin is a product of the pineal gland, which regulates the circadian cycle. Neurotoxicity is the most important side effect of methamphetamine (Met) abuse during pregnancy. This study aimed to explore the effect of Met exposure during gestation and lactation periods on the learning and memory of offspring mice. The protective effect of melatonin and the role of oxidative stress and acetylcholinesterase were also investigated.
The pregnant mice were randomly divided into 2 groups. Saline or Met (5 mg/kg) was injected daily during pregnancy and lactation. After the lactation period, the offspring mice of each group were divided into 2 subgroups, and saline or melatonin (10 mg/kg) was orally (gavage) administered to the offspring mice from the post-delivery (PD) day 21 up to PD Day 60. The offspring mice were examined in the passive avoidance (PA) test. Finally, oxidative stress markers and acetylcholinesterase (AchE) activity were measured in the brains.
FINDINGS/RESULTS: As a result, Met decreased delay and light time while increasing the frequency of entry and time in the dark region of PA. However, melatonin alleviated the impairing effect of Met on PA performance. Meanwhile, the administration of Met increased malondialdehyde while decreasing superoxide dismutase and thiol content. Furthermore, AchE activity was significantly increased in Met-treated mice. Melatonin reversed the levels of antioxidants, lipid peroxidation, and AchE activity in the brain.
Together, these results suggested that melatonin may be a potential therapeutic agent for alleviating Met-induced memory impairment by restoring redox hemostasis and AchE.
褪黑素是松果体分泌的一种产物，可调节昼夜节律。神经毒性是孕期滥用甲基苯丙胺（Met）最重要的副作用。本研究旨在探讨孕期和哺乳期暴露于Met对仔鼠学习和记忆的影响。同时还研究了褪黑素的保护作用以及氧化应激和乙酰胆碱酯酶的作用。
将怀孕小鼠随机分为2组。在怀孕和哺乳期每天注射生理盐水或Met（5 mg/kg）。哺乳期结束后，将每组的仔鼠再分为2个亚组，从分娩后（PD）第21天至PD第60天，对仔鼠口服（灌胃）生理盐水或褪黑素（10 mg/kg）。在被动回避（PA）试验中对仔鼠进行检测。最后，测定大脑中的氧化应激标志物和乙酰胆碱酯酶（AchE）活性。
结果显示，Met减少了延迟时间和光照时间，同时增加了进入PA黑暗区域的频率和时间。然而，褪黑素减轻了Met对PA表现的损害作用。同时，给予Met会增加丙二醛含量，同时降低超氧化物歧化酶和硫醇含量。此外，Met处理的小鼠中AchE活性显著增加。褪黑素逆转了大脑中抗氧化剂水平、脂质过氧化和AchE活性。
综上所述，这些结果表明褪黑素可能是一种潜在的治疗药物，可通过恢复氧化还原稳态和AchE来减轻Met诱导的记忆损害。
